Potassium Carbonate → Ethyl 1-(3-phenylpropyl)pyrazole-4-carboxylate

HRID 2250336Notes

Reaction equation

HRID 2250336 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CC(C)=O>[C:21]1([CH2:20][CH2:19][CH2:18][N:1]2[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:3]=[N:2]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12503(3-Bromopropyl)benzeneHCID 142179ethyl 1H-pyrazole-4-carboxylate

Product 1

HCID 21958678Ethyl 1-(3-phenylpropyl)pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of ethyl 4-pyrazole carboxylate (3.57 mmol) in acetone (30 ml) was added potassium carbonate (35.7 mmol) and 1-bromo-3-phenylpropane (3.57 mmol). The suspension was refluxed overnight, after which the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and water, the organic layer dried over magnesium sulfate, filtered, and the filtrate evaporated under reduced pressure to give an oil, which was purified by preparative TLC, to give ethyl 1-(3-phenylpropyl)pyrazole-4-carboxylate. b) The ester was then dissolved in methanol (30 ml), and potassium hydroxide (1.5 g) added. The mixture was refluxed for 5 hours under nitrogen, then the solvent removed under reduced pressure. The residue was partitioned between methylene chloride and water. The aqueous layer was separated and acidified to pH 1-2 with 6N hydrochloric acid, then extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, and the solvent removed under reduced pressure, to give 1-(3-phenylpropyl)pyrazole-4-carboxylic acid. c To a solution of 1-(3-phenylpropyl)pyrazole-4-carboxylic acid (300 mg, 1.30 mmol) in N,N-dimethylformamide (7 ml) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (300 mg). The suspension was stirred at room temperature until all solid was dissolved, then 5,6-diamino-1,3-dipropyl-1,3-dihydropyrimidine-2,4-dione (450 mg) added, and the reaction mixture stirred at room temperature overnight. 2N sodium hydroxide (10 ml) was then added, and the suspension heated at 120° C. for 2 hours. The reaction mixture was cooled in ice water and acidified to pH 2-3. The mixture was partitioned between water and ethyl acetate, and the ethyl acetate layer and any solid material was washed with water, and the solvent removed under reduced pressure. The residue was triturated with ether, giving pure product, 8-[1-(3-phenylpropyl)pyrazol-4-yl)]-1,3-dipropyl-1,3,7-trihydropurine-2,6-dione.

Workup

  1. temperatureThe suspension was refluxed overnight
  2. customafter which the solvent was removed under reduced pressure
  3. customThe residue was partitioned between ethyl acetate and water
  4. dry with materialthe organic layer dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe filtrate evaporated under reduced pressure
  7. customto give an oil, which
  8. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-fe7ec1afbad6418c976848f614132aeb
Source dataset
uspto-grants-2008_01
Patent number
US07317017B2

Reaction notes

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